tbuckley/cabot-search huggingface dataset:
Quantitative proteomics landscape and association with BASP1 and breast cancer metastasis.
Authors: Jaspreet Kaur, Marie Austdal, Sung Yun Jung, Emiel Janssen, Håvard Søiland, Ritu Aneja
Journal: Journal of Clinical Oncology (2022)

1090 Background: Tumor recurrence and metastatic progression remain the leading cause for breast cancer related mortalities. The study aimed to identify differences in proteomics landscape in serum between (i) healthy controls and breast cancer patients, (ii) baseline samples at time of diagnosis from patients that later developed metastases versus those that did not and, (iii) baseline samples presented after completed treatment versus the samples collected before patients developed metastasis. Methods: We performed mass spectrometery-based proteome profiling of 100 serum samples from 51 breast cancer patients and 27 healthy donors. Of the 51-breast cancer patients, 29 patients did not metastasize, and 22 patients had a metastatic recurrence. Each of the 22 breast cancer patients with metastasis had 2 samples-one collected within a year of diagnosis and second one collected within a year before the patient developed metastases. Intensity-based absolute quantification (iBAQ) method was employed to convert recovered peptide information to quantificational gene protein product and then normalized to final quantificational value using an in-housed software. Protein values were normalized using z-score before differential expression analyses. FDR &lt; 0.1 and a p-value &lt; 0.05 was used as the cutoff to identify differentially expressed proteins. Results: We identified 1177 proteins in total from 100 serum samples of healthy women and breast cancer patients. PCA analysis revealed a complete separation of the breast cancer and healthy control samples. However, we found overlapping but distinct groups of metastatic and non-metastatic samples. We found 179 proteins to be differentially expressed between normal healthy control samples and baseline breast cancer samples irrespective of their metastatic status. Upon comparing baseline breast cancer samples that metastasized with breast cancer samples that did not metastasize, we found BASP1 as the top-ranked gene that was significantly upregulated in metastatic samples. We did not find any significant differences between paired baseline samples collected at diagnosis and pre-metastatic samples collected before the patient developed metastasis. Conclusions: Our results show distinct proteomic profiles exist between breast cancer and normal healthy control samples. Further studies are required to confirm if serum BASP1 can be used as a putative biomarker for predicting metastatic risk in breast cancer patients.
OTHR-21. Ethical reflections via the dilemma method in a pediatric neuro-oncology department
Authors: Antoinette Schouten- van Meeteren, Simone Lenting, Mirjam Sulkers, Marianne van de Wetering
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: Professional care for children with a brain tumor can bring considerable ethical questions in clinical practice. These questions can be burdensome and cause distress among professionals, parents and patients. Awareness and skills to bring these aspects into a respectful discussion among colleagues can be meaningful and alleviate the distress. Our objective is to give overview of the ethical case deliberations which took place during a monthly multidisciplinary meeting on the pediatric neuro-oncology department. METHOD: To describe the type of ethical case deliberations as spontaneously proposed and selected by the team members for discussion. To identify main values in the care process for professionals via the dilemma method in monthly meetings led by a trained facilitator. RESULTS: The monthly meetings were visited regularly by 9-14 diverse professionals (median 10) of the team: nurses, oncologists, social worker, psychologist, educational specialist. The selected moral questions concerned children with a brain tumor between 4-13 year old (median 9) with following ten subjects: 3 not sharing the infaust prognosis with a child, 2 avoiding medical care in follow up /treatment, 2 cultural different approach for food and drink intake, 2 crossing professional boundaries and 1 time worries about emotional safety of a child. The main values that were recognized to play crucial role in the care process were honesty, respect, autonomy, quality of life, health, tolerance, courage and safety. The participants felt supported in their professional skills by sharing reflections on personal moral considerations and by openly discussing different views and experiences of other participants. CONCLUSION: The monthly ethical case discussions disclose high lights in the burden of professional care in pediatric neuro-oncology. These meetings about moral questions are supportive in the competence of the professionals to recognize and communicate about these important dilemmas.
Rural disparities in oncology patient portal enrollment and use.
Authors: Bonny Morris, Umit Topaloglu, Glenn Jay Lesser, Roy E. Strowd, Kathryn E. Weaver, Derek Sean Falk, Ronny A. Bell
Journal: Journal of Clinical Oncology (2022)

6557 Background: Patient portals support patient access, engagement, and care coordination, yet could also widen the digital divide and exacerbate disparities among vulnerable populations. There is emerging evidence that racial/ethnic minority patients are less likely to use portals, yet prior research has not examined potential rural differences. We identified sociodemographic factors associated with portal enrollment and use among a racially and geographically diverse population of cancer patients. Methods: We retrospectively examined portal enrollment and use at an NCI-designated comprehensive cancer center from January 2015 until February 2022 among patients 18+ years old with a neoplastic disease diagnosis (ICD-10-CM C00-D49). Potential predictors included gender, race/ethnicity, marital status, age, rural (Rural-Urban Continuum Codes [RUCC] 4-9) vs nonrural (RUCC 1-3) residence, residential distance from the cancer center, and time since diagnosis. We used multivariable logistic regression to generate odds ratios (ORs) for portal enrollment and having ever sent a portal message, and Poisson regression to determine incidence rate ratios (IRRs) for number of logins and number of healthcare team interactions (portal messages or appointment requests), controlling for ICD-10 diagnosis (SAS 9.4). Results: We identified 11,333 patients (average age 67 years, 59% female, 24% rural, 10% Non-Hispanic Black, 1% Hispanic, 20% non-melanoma skin cancer, 14% breast cancer, 9% lung cancer). 36% of patients had enrolled in the portal, and of these, 80% had sent at least one message. Patients logged in a median of 203.5 times and had a median of 19 portal interactions. Rural residents were less likely to enroll in the portal than urban patients (28% vs 38%, p &lt; 0.0001). Non-Hispanic Black patients and Hispanic/Latinx patients were less likely to enroll in the portal compared with non-Hispanic White patients (22% and 27%, respectively, vs 38.5%, p &lt; 0.0001). Women, younger patients, more recently diagnosed cancer patients, and patients who were married/ partnered were significantly more likely to enroll. In multivariable analysis controlling for cancer type, rural patients were half as likely to enroll in the portal (OR: 0.48 [0.43-0.54]). Among those enrolled, rural residents were 25% less likely to have ever sent a portal message (OR: 0.75 [(0.62-0.92]), and had nearly half the login and interaction rates (IRR: 0.66 [0.66-0.67]; IRR: 0.58 [0.58-0.59], respectively). Patients who were Non-Hispanic Black, Hispanic, or unmarried were also significantly less likely to enroll or engage in the portal. Conclusions: Patient portals remain underutilized among cancer patients, despite an increased reliance on virtual communications in the COVID era. Interventions to support portal engagement among rural residents and racial/ethnic minority patients are needed to avoid potentially exacerbating health disparities.
Snake Venom Hydrogels as a Rapid Hemostatic Agent for Uncontrolled Bleeding
Authors: Ramanathan Yegappan, Jan Lauko, Zhao Wang, Martin F. Lavin, Amanda W. Kijas, Alan E. Rowan
Journal: Advanced Healthcare Materials (2022)

Uncontrolled bleeding from traumatic injury remains the leading cause of preventable death with loss of balance between blood clotting (coagulation) and blood clot breakdown (fibrinolysis). A major limitation of existing hemostatic agents is that they require a functioning clotting system to control the bleeding and are largely based on gauze delivery scaffolds. Herein, a novel rapid wound sealant, composed of two recombinant snake venom proteins, the procoagulant ecarin, to rapidly initiate blood clotting and the antifibrinolytic textilinin, to prevent blood clot breakdown within a synthetic thermoresponsive hydrogel scaffold is developed. In vitro, it is demonstrated that clotting is rapidly initiated with only nanomolar concentrations of venom protein and clot breakdown is effectively inhibited by textilinin. A stable clot is formed within 60 s compared to normal clot formation in 8 min. In vivo studies reveal that the snake venom hydrogel rapidly controls warfarin-induced bleeding, reducing the bleed volume from 48% to 12% and has demonstrated immune compatibility. A new class of hemostatic agents that achieve formation of rapid and stable blood clots even in the presence of blood thinners is demonstrated here.
ASCO oral presenters five years later: Leaks in the pipeline?
Authors: Forrest Kwong, Kimberly Lerner, Derrick L. Tao, Sarah Patel, Vinay Prasad
Journal: Journal of Clinical Oncology (2022)

11019 Background: There is growing awareness of the challenges of retaining oncologists engaged in research, and this leaky academic pipeline is most notable for women in medicine. Studying academic oncologists is challenging due to their many affiliations, but with an estimated attendance of over 30,000 oncologists, the ASCO annual meeting is a highly sought-after stage for presenting new research. To better understand the continued research engagement of oncologists active in research, we used public data from ASCO annual meetings to follow a cohort of oral abstract presenters over 5 years. Methods: To define our initial cohort of oncologists engaged in research, we used the 2016 ASCO Annual Meeting Digital Program to identify first author oral abstract presenters. We tracked if each presenter was subsequently listed as an author of any research type (oral abstract session, poster session, education session, etc.) at the 2017, 2018, 2019, 2020 and 2021 ASCO conferences. We then filtered out researchers who were not listed as authors at ASCO in consecutive years to look at only those researchers who continued to have active ASCO involvement. To evaluate by gender, each presenter’s name was referenced with the publicly available Wiki-Gendersort tool for an unbiased assignment. Results: 209 first author oral abstract presenters were identified at the 2016 ASCO conference. We found that 67.9% of the initial 209 researchers were listed as authors at ASCO in 2017, 55.5% continued to be authors in 2018, 46.9% in 2019, 42.6% in 2020, and only 38.3% were still listed as authors 5 years later in 2021. When looking at sustained first authorship, 8.1% of the initial 209 research cohort continued to be listed as first authors for 5 consecutive years through 2021. We also looked at the breakdown of other types of ASCO presentations and found that 122 of the initial 209 research cohort presented posters in 2016. Of these 122 researchers, 60 (49.2%) remained authors of posters throughout the consecutive 5 years. This is significantly higher than the number of researchers who continued to author oral abstracts in 2021 49.2% vs. 3.8% (P &lt; 0.0001). When evaluating the differences between gender, there were approximately twice as many men presenters as women (122 men vs 65 women; 22 names were unisex or unknown). The rate of retention was similar for men (47 of the initial 122 males, 38.5%) and women (25 of the initial 65 females, 38.5%) at 5 years (P = 1). Conclusions: We conducted a descriptive study evaluating the rate of sustained activity in academic oncology over 5 years. Our research suggests that about one-third of ASCO presenters will continue to have sustained yearly authorship at 5 years post-oral abstract presentation. Compared to men, the leaky academic pipeline is comparable for women in the 5 years following an oral abstract presentation at ASCO.
Video Endoscopic Inguinal Lymphadenectomy (VEIL) vs. Open Inguinal Lymphadenectomy (OILND) for penile carcinoma: A retrospective study
Authors: R. Zanotti, E. Silveira Brazão Jr., J. Menezes, R. Ribeiro Meduna, J.Q. Caon Nobre, V. Espinheira, L. Fornazieri, M. Murce Rocha, D. Coser Gomes, R.S. Madeira Campos, W. Henriques Da Costa, W. Bachega Jr., J. Ribeiro Zanotti, L. Leitão, C.A. Ricetto Sacomani, T.B. Marques Santana, S. Cássio Zequi
Journal: European Urology (2022)
Sex-related proteomic differences of the athlete's heart
Authors: BA Barta, A Olah, O Bottlik, M Ruppert, AA Sayour, B Merkely, O Schilling, T Radovits
Journal: Cardiovascular Research (2022)

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Bolyai János Research Scholarship - BO/00837/21 to O.A., National Research, Development and Innovation Office (NKFIH) of Hungary - K135076 to B.M. Introduction Regular physical activity results in characteristic structural and functional changes in the heart, which are collectively referred to as the athlete’s heart. However, the extent of exercise-induced left ventricular (LV) hypertrophy and functional changes show significant differences between men and women, the molecular background of which is not fully elucidated. Purpose The aim of this study was to provide a proteomic characterization of long-term, intense exercise-induced LV myocardial hypertrophy in a rat model, with a focus on sex-related differences. Methods Our rats were divided into trained (FEx) and control female (FCo) as well as trained (MEx) and control male (MCo) groups. In the trained groups, athlete’s heart was induced by a 12-week swimming protocol. Myocardial hypertrophy was confirmed by echocardiography and functional adaptation by pressure-volume analysis. Proteomic measurements based on liquid chromatograph-coupled mass spectrometry were performed on proteins isolated from our LV myocardial samples. Results Echocardiography and post-mortem myocardial mass showed significant LV hypertrophy in both sexes, which was more pronounced in female animals (tibial length normalized LV muscle mass: + 17.4% MEx vs. MCo, + 31.0% FEx vs. FCo). LV contractility increased to the same extent in both sexes. Relative expression of 3074 proteins were determined by proteomics. There was a significant change in expression of 229 proteins in males and 599 in females compared to the level of same-sex controls. Based on our gene ontological analysis, physiological LV remodeling in females is characterized by increased expression of proteins in cellular respiration and fatty acid oxidation, whereas in males, proteins that bind to the actin cytoskeleton is primarily increased. Conclusions Our data suggests that physiological LV hypertrophy resulting from regular, balanced exercise is associated with sex-specific changes in the myocardial proteome. Our results contribute to the understanding of the development of physiological myocardial hypertrophy.
Precision Phenotyping of Dilated Cardiomyopathy Using Multidimensional Data
Authors: Upasana Tayal, Job A.J. Verdonschot, Mark R. Hazebroek, James Howard, John Gregson, Simon Newsome, Ankur Gulati, Chee Jian Pua, Brian P. Halliday, Amrit S. Lota, Rachel J. Buchan, Nicola Whiffin, Lina Kanapeckaite, Resham Baruah, Julian W.E. Jarman, Declan P. O’Regan, Paul J.R. Barton, James S. Ware, Dudley J. Pennell, Bouke P. Adriaans, Sebastiaan C.A.M. Bekkers, Jackie Donovan, Michael Frenneaux, Leslie T. Cooper, James L. Januzzi, John G.F. Cleland, Stuart A. Cook, Rahul C. Deo, Stephane R.B. Heymans, Sanjay K. Prasad
Journal: Journal of the American College of Cardiology (2022)

Dilated cardiomyopathy (DCM) is a final common manifestation of heterogenous etiologies. Adverse outcomes highlight the need for disease stratification beyond ejection fraction.
Clinical artificial intelligence quality improvement: towards continual monitoring and updating of AI algorithms in healthcare
Authors: Jean Feng, Rachael V. Phillips, Ivana Malenica, Andrew Bishara, Alan E. Hubbard, Leo A. Celi, Romain Pirracchio
Journal: npj Digital Medicine (2022)

Machine learning (ML) and artificial intelligence (AI) algorithms have the potential to derive insights from clinical data and improve patient outcomes. However, these highly complex systems are sensitive to changes in the environment and liable to performance decay. Even after their successful integration into clinical practice, ML/AI algorithms should be continuously monitored and updated to ensure their long-term safety and effectiveness. To bring AI into maturity in clinical care, we advocate for the creation of hospital units responsible for quality assurance and improvement of these algorithms, which we refer to as "AI-QI" units. We discuss how tools that have long been used in hospital quality assurance and quality improvement can be adapted to monitor static ML algorithms. On the other hand, procedures for continual model updating are still nascent. We highlight key considerations when choosing between existing methods and opportunities for methodological innovation.
Need for organ preservation in postchemotherapy retroperitoneal lymph node dissection (PC-RPLND).
Authors: Tim Nestler, Pia Paffenholz, David Pfister, Yasmine Maatoug, Yue Che, Andreas Hiester, Peter Albers, Axel Heidenreich
Journal: Journal of Clinical Oncology (2022)

5031 Background: The aim ofPC-RPLND for advanced nonseminomatous germ cell tumors is to resect all remaining metastatic tissue. So far, the resection of adjacent visceral or vascular organs is also commonly performed to achieve complete resection of the residual mass. To determine the possibility of more organ preservation, we aimed to analyze the pathohistology of patients with adjunctive surgery as the frequency of metastatic involvement in those organs with teratoma or vital cancer is currently unknown. Methods: We reviewed a cohort of 1204 patients who underwent PC-RPLND between 2008 and 2021 as a 2-center study and identified 242 (20.1%) cases of adjunctive surgery during PC-RPLND. We analysed the pathohistological presence of germ cell tumor elements in the resected organs: viable tumor (V), teratoma (T) or necrosis / fibrosis (N). Surgery associated complications were reported according to the Clavien-Dindo classification. Outcomes of subgroups were compared by using log-rank test. Results: V, T and N were present in 54 (22%), 94 (39%) and 94 (39%) of all patients with adjunct resected organs. In 242 patients, 325 adjunct organs were resected with 66 (27.3%) of these patients receiving a resection of multiple organs. The kidney was the most often resected organ (n = 77; V: 29% T: 39% N: 32%), followed by V. Cava (n = 67; V: 25% T: 36%, N: 39%) and partial liver resections (n = 50; V: 16%, T: 30%, N: 54%). Postoperative complications occurred in 30% of which 22% were Clavien grade III-V, showing no significant differences between V, T and N; p = 0.093. 27% of all patients suffered from a relapse during a median follow-up of 22 months [0-180]. Patients with T or V in the resected specimens had a significantly reduced 5-year RFS compared to patients with only N (39%, 81%, p &lt; 0.001). Conclusions: This study shows tremendous need for more organ preservation as 40% of all resections of adjunct organs are oncologically unnecessary due to the presence of N only in the pathological specimens. Therefore, in case of doubt, we should increase intraoperative frozen section to avoid oncologically unnecessary adjunctive surgeries, especially nephrectomies and vascular resections. Additionally, serological or image-based means for a more accurate presurgical workup are required to spare patients with N from PC-RPLND in general.
Gremlin1 is a therapeutically targetable FGFR1 ligand that regulates lineage plasticity and castration resistance in prostate cancer
Authors: Chaping Cheng, Jinming Wang, Penghui Xu, Kai Zhang, Zhixiang Xin, Huifang Zhao, Zhongzhong Ji, Man Zhang, Deng Wang, Yuman He, Na Jing, Liancheng Fan, Kaiyuan Liu, Fei Li, Chengcheng Liu, Yiming Gong, Suli Cui, Zhe Sun, Di Sun, Xinlai Yao, Hongjun Li, Jian Zhang, Pengcheng Zhang, Baijun Dong, Wei Xue, Xueming Qian, Wei-Qiang Gao, Helen He Zhu
Journal: Nature Cancer (2022)
Microfluidics Fabrication of Micrometer‐Sized Hydrogels with Precisely Controlled Geometries for Biomedical Applications
Authors: Zhenyang Wei, Shiqi Wang, Jouni Hirvonen, Hélder A. Santos, Wei Li
Journal: Advanced Healthcare Materials (2022)

Micrometer-sized hydrogels are cross-linked three-dimensional network matrices with high-water contents and dimensions ranging from several to hundreds of micrometers. Due to their excellent biocompatibility and capability to mimic physiological microenvironments in vivo, micrometer-sized hydrogels have attracted much attention in the biomedical engineering field. Their biological properties and applications are primarily influenced by their chemical compositions and geometries. However, inhomogeneous morphologies and uncontrollable geometries limit traditional micrometer-sized hydrogels obtained by bulk mixing. In contrast, microfluidic technology holds great potential for the fabrication of micrometer-sized hydrogels since their geometries, sizes, structures, compositions, and physicochemical properties can be precisely manipulated on demand based on the excellent control over fluids. Therefore, micrometer-sized hydrogels fabricated by microfluidic technology have been applied in the biomedical field, including drug encapsulation, cell encapsulation, and tissue engineering. This review introduces micrometer-sized hydrogels with various geometries synthesized by different microfluidic devices, highlighting their advantages in various biomedical applications over those from traditional approaches. Overall, emerging microfluidic technologies enrich the geometries and morphologies of hydrogels and accelerate translation for industrial production and clinical applications.